研究人员发现，大麻使用后的止痛效应受药物中与甘氨酸受体（GlyR）离子通道相连的活性成分四氢大麻酚（THC）所控制，因此，有望研制出只具有止痛效应的四氢大麻酚变体，新成果发表在4月在线出版的《自然—化学生物学》期刊上。基于大麻的药物有兴奋和损伤精神活动的副作用，从而限制了这类药物未来发展为止痛药的可能；但新研究显示，修改其中的成分可研制出副作用最小化的新药。
大麻即有止痛也有影响精神活性的效应，这两种效应均源于它的活性成分四氢大麻酚。科学家们发现，大麻的精神效应受到与大麻受体CB1R联接的四氢大麻酚所控制，但他们尚不清楚与止痛效应相关的机制。Li Zhang和同事发现了与跨膜区的GlyR相连接的四氢大麻酚，以及发生在四氢大麻酚化学组分和受体间的氢键相互作用。他们还发现，去除四氢大麻酚的羟基可导致一种不能激活GlyR的化合物。这些数据表明，有可能研制出只激活GlyRs但没有CB1R活性的四氢大麻酚止痛药。（生物谷Bioon.com）
生物谷推荐原文出处：
Nature Chemical Biology doi:10.1038/nchembio.552
Cannabinoid potentiation of glycine receptors contributes to cannabis-induced analgesia
Wei Xiong,1 KeJun Cheng,2 Tanxing Cui,3, 4, 5 Grzegorz Godlewski,6 Kenner C Rice,2 Yan Xu3, 4, 5 & Li Zhang1
Cannabinoids enhance the function of glycine receptors (GlyRs). However, little is known about the mechanisms and behavioral implication of cannabinoid-GlyR interaction. Using mutagenesis and NMR analysis, we have identified a serine at 296 in the GlyR protein critical for the potentiation of IGly by Δ9-tetrahydrocannabinol (THC), a major psychoactive component of marijuana. The polarity of the amino acid residue at 296 and the hydroxyl groups of THC are critical for THC potentiation. Removal of the hydroxyl groups of THC results in a compound that does not affect IGly when applied alone but selectively antagonizes cannabinoid-induced potentiating effect on IGly and analgesic effect in a tail-flick test in mice. The cannabinoid-induced analgesia is absent in mice lacking α3GlyRs but not in those lacking CB1 and CB2 receptors. These findings reveal a new mechanism underlying cannabinoid potentiation of GlyRs, which could contribute to some of the cannabis-induced analgesic and therapeutic effects.
